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<p>DNA methylation is vital for development and diseases, yet no spatial DNA methylation profiling technology has been reported. Here we developed spatial 5mC-seq (SmC-seq), a microfluidic-based method providing unbiased genome-wide methylome at near single-cell resolution. Applying SmC-seq to mouse post-implantation development revealed a clear spatial heterogenous pattern of DNA methylation in inner cell mass-derived tissues. We identified a two-layer organization in the E8.5 ectoplacental cone with distinct methylation and proliferation states. Unexpectedly, a portion of maternal tissue with low DNA methylation level, enriched for nutrient-supplier progenitors, is observed in the middle region of decidua post-implantation. The hypomethylated regions in the nutrient-supplier progenitor cluster are associated with cell proliferation. Notably, the genes associated with hypomethylated regions in mature nutrient-supplier cluster are enriched in exocytosis and nutrient synthesis, linked to nutrient provision for embryogenesis before placental function. In summary, SmC-seq enables spatial DNA methylation mapping, advancing our understanding of biological events.</p>

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Spatial 5mC-seq profiling of embryos and decidua after implantation in mammals

  • 期刊论文

  • 发表日期：

    2026年4月27日

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  • Xun Shan,
  • Yimin Tang,
  • Jinzhou Hu,
  • Mingyuan Bian,
  • Xuelong Yao,
  • Lei Gao,
  • Jiang Liu

摘要

DNA methylation is vital for development and diseases, yet no spatial DNA methylation profiling technology has been reported. Here we developed spatial 5mC-seq (SmC-seq), a microfluidic-based method providing unbiased genome-wide methylome at near single-cell resolution. Applying SmC-seq to mouse post-implantation development revealed a clear spatial heterogenous pattern of DNA methylation in inner cell mass-derived tissues. We identified a two-layer organization in the E8.5 ectoplacental cone with distinct methylation and proliferation states. Unexpectedly, a portion of maternal tissue with low DNA methylation level, enriched for nutrient-supplier progenitors, is observed in the middle region of decidua post-implantation. The hypomethylated regions in the nutrient-supplier progenitor cluster are associated with cell proliferation. Notably, the genes associated with hypomethylated regions in mature nutrient-supplier cluster are enriched in exocytosis and nutrient synthesis, linked to nutrient provision for embryogenesis before placental function. In summary, SmC-seq enables spatial DNA methylation mapping, advancing our understanding of biological events.